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1.
Newer Therapies in Psoriasis.
Marson, JW, Snyder, ML, Lebwohl, MG
The Medical clinics of North America. 2021;(4):627-641
Abstract
Psoriasis is a systemic inflammatory condition that negatively affects the quality of life and medical health of 125 million individuals globally. Although psoriasis has historically been viewed as a skin-limited disease and managed with topical agents (eg, coal tar, corticosteroids, and vitamin D analogues), the recontextualization of psoriasis as a systemic condition involving multiple organ systems has prompted the development of numerous immunomodulating, systemic agents with more targeted mechanisms of action. This article briefly discusses the indications and nuances of new and developing therapeutic agents for psoriasis management.
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2.
Optimization of biologics to reduce treatment failure in inflammatory bowel diseases.
Bourchany, A, Gilletta De Saint-Joseph, C, Breton, A, Barreau, F, Mas, E
Current opinion in pharmacology. 2020;:51-58
Abstract
Moderate to severe inflammatory bowel disease patients can fail to respond to conventional therapy and/or to biologic treatment. In the era of TNFα antagonists and other non-anti-TNF biologic drugs, it is important to review the literature on biologic treatment failure, which could be defined as primary non-response, secondary loss of response and intolerance. Therapeutic drug monitoring (TDM), that is, drug trough level and antidrug antibodies, should enable to determine the mechanisms of treatment failure and to optimize drug efficacy. There is a consensus on reactive TDM at the time of loss of response. Proactive TDM could be of interest during induction and/or maintenance, but randomized controlled trials are required.
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3.
Muscle, Bone, and Fat Crosstalk: the Biological Role of Myokines, Osteokines, and Adipokines.
Kirk, B, Feehan, J, Lombardi, G, Duque, G
Current osteoporosis reports. 2020;(4):388-400
Abstract
PURPOSE OF REVIEW Skeletal muscle and bone are connected anatomically and physiologically, and play a crucial role in human locomotion and metabolism. Historically, the coupling between muscle and bone has been viewed in light of mechanotransduction, which dictates that the mechanical forces applied to muscle are transmitted to the skeleton to initiate bone formation. However, these organs also communicate through the endocrine system, orchestrated by a family of cytokines namely myokines (derived from myocytes) and osteokines (derived from bone cells). A third player in this biochemical crosstalk is adipose tissue and the secretion of adipokines (derived from adipocytes). In this review, we discuss the bidirectional effects of myokines and osteokines on muscle and bone metabolism, and the impact of adipokines on both of these secretory organs. RECENT FINDINGS Several myokines, notably, IL6, irisin, IGF-1, BDNF, myostatin, and FGF2 exert anabolic/catabolic effects on bone, while the osteokines osteocalcin and sclerostin have shown to induce muscle anabolism and catabolism, respectively. Adipokines, such as leptin, resistin, adiponectin, and TNFα (released from adipose tissue), can also modulate muscle and bone metabolism. Contrarily, exercise-mediated release of lipolytic myokines (IL6, irisin, and LIF) stimulates thermogenesis by promoting the browning of adipocytes. Myokines, osteokines, and adipokines exert autocrine/paracrine effects locally as well as through the endocrine system, to regulate muscle, bone, and fat metabolism. Reductions in physical activity and increases in energy intake, both linked with aging, leads to adipocyte hypertrophy and the recruitment of immunological cells (macrophages). In turn, this releases pro-inflammatory adipokines which induces chronic low-grade inflammation (LGI), a key player in the pathology of several diseases. However, exercise-induced stimulation of bioactive cytokines, through muscle-bone-fat crosstalk, increases muscle anabolism, bone formation, mitochondrial biogenesis, glucose utilization, and fatty acid oxidation, and attenuates chronic LGI.
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4.
Anti-TNF combination therapy in inflammatory bowel disease: de novo or selective?
Macaluso, FS, Orlando, A
Minerva gastroenterologica e dietologica. 2019;(4):291-297
Abstract
Anti-TNFs still remain the backbone of advanced therapies in inflammatory bowel diseases, but their efficacy is not universal and tends to diminish over time. As a consequence, there is the need for optimization of these treatments, and the use of combination therapy - i.e. an anti-TNF plus an immunosuppressant - is one of the main strategies. The rationale for this approach lies in the evidence that the immunosuppressant reduces the formation of antibodies directed against the anti-TNF, thus avoiding the reduction or elimination of circulating drug levels, and in the combination of the therapeutic effect of two drugs. Nowadays, two different combination therapies should be distinguished. In the "de novo" combination therapy, the anti-TNF is used in combination with an immunosuppressant from the beginning of the treatment, in order to prevent the formation of anti-drug antibodies. In the "selective" combination therapy, the immunosuppressant is added at a later time in patients who experience a loss of response during anti-TNF monotherapy due to the development of anti-drug antibodies. The purpose of this review is to summarize the available evidence on both de novo and selective combination therapy. In addition, we will express our point of view on the choice between these two different treatment modalities.
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5.
Use of biosimilars in inflammatory bowel disease: a position update of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).
Fiorino, G, Caprioli, F, Daperno, M, Mocciaro, F, Principi, M, Viscido, A, Fantini, MC, Orlando, A, Papi, C, Annese, V, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2019;(5):632-639
Abstract
The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars.
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6.
Tumor necrosis factor-α and diabetic retinopathy: Review and meta-analysis.
Yao, Y, Li, R, Du, J, Li, X, Zhao, L, Long, L, Li, D, Lu, S
Clinica chimica acta; international journal of clinical chemistry. 2018;:210-217
Abstract
BACKGROUND Tumor necrosis factor-alpha (TNF-α) is produced by multinuclear giant cells and acts as local intensification signals in pathological processes associated with chronic eye inflammation. This meta-analysis was performed to provide a better understanding of the relationship between TNF-α and diabetic retinopathy (DR). METHOD Online electric databases were searched to retrieve all relevant articles published before October 2017. The standard mean difference (SMD) and their 95% confidence intervals (CI) were included and then pooled with a random effects model. RESULTS A total of 16 articles with 1286 participants were included in this meta-analysis. No difference in the level of TNF-α was found between DR patients and healthy controls (SMD = 0.39, 95% CI = -0.09 to 0.68, P = 0.01). Subgroup analysis showed that with respect to the level of TNF-α, the association was significant for studies conducted in Europe (SMD: 0.57, 95% CI: 0.11-1.02, P = 0.01), patients with type 1 DM (SMD: 1.06, 95% CI: 0.09-2.04, P = 0.03), studies based on serum samples (SMD: 0.57, 95% CI: 0.12-1.02, P = 0.01) and studies with a sample size >50 (SMD: 0.39, 95% CI: 0.03-0.75, P = 0.04). CONCLUSION The results this meta-analysis indicated that the level of TNF-α in DR patients was significantly different from that in the healthy controls, so TNF-α represents a candidate biomarker for DR.
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7.
Outcome of pregnancy and neonatal complications with anti-tumor necrosis factor-α use in females with immune mediated diseases; a systematic review and meta-analysis.
Komaki, F, Komaki, Y, Micic, D, Ido, A, Sakuraba, A
Journal of autoimmunity. 2017;:38-52
Abstract
BACKGROUND Immune mediated diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) commonly affect young and adolescent females. Anti-tumor necrosis factor (TNF)-α agents are increasingly used to treat these conditions, but their safety during pregnancy remains unclear. OBJECTIVES To evaluate the risk of pregnancy related outcomes in patients with various immune mediated diseases treated with anti-TNF-α agents. METHODS Electronic databases were searched for studies assessing the outcome of pregnancy in female patients with various immune mediated diseases who were treated with anti-TNF-α agents. Direct and network meta-analyses were performed between anti-TNF-α users, non-users, and the general population. RESULTS Thirteen studies (including RA, IBD and various immune mediated diseases) were identified. Among the studies that compared the outcome between anti-TNF-α users and the general population, anti-TNF-α users had a non-significant trend towards reduced rate of live birth (odds ratio (OR) = 0.38 (P = 0.081), 95% confidence interval (CI) = 0.13-1.13) and were at significantly increased risk of preterm birth (OR = 2.62 (P < 0.0001), 95% CI = 2.12-3.23), spontaneous abortion (OR = 4.08 (P = 0.033), 95% CI = 1.12-14.89) and low birth weight (OR = 5.95 (P = 0.032), 95% CI = 1.17-30.38) compared to the general population. Risk of anomalies was not elevated (OR = 1.46 (P = 0.18), 95% CI = 0.84-2.56). Among the studies that compared the outcome between anti-TNF-α users and non-users, there were no significant differences in the rates of live birth and pregnancy related complications. Among the studies that compared the outcome between non-anti-TNF-α users and the general population, risk of spontaneous abortion was elevated (OR = 2.60 (P = 0.033), 95% CI = 1.08-6.27), but there were no significant differences in the rates of live birth and other pregnancy related complications. Network meta-analysis confirmed the rank order of all outcomes as general population, non-users and users of anti-TNF-α agents (ascending order based on safety). CONCLUSIONS Female patients with immune mediated diseases treated with anti-TNF-α agents were at significantly increased risks of preterm birth, spontaneous abortion and low birth weight compared to the general population, but had comparable outcomes with non-users. These results provide useful information for female patients in their reproductive age and raise awareness of the conditions that they are facing among clinicians managing their care.
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8.
Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.
Zhai, J, Bo, Y, Lu, Y, Liu, C, Zhang, L
PloS one. 2017;(1):e0170172
Abstract
BACKGROUND/OBJECTIVE Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10) has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases. METHODS Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs). The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C reactive protein (CRP). RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software. RESULTS Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87) μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24) pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17) mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16) pg/ml, I2 = 84%]. CONCLUSIONS CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.
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9.
Genetics and immunodysfunction underlying Behçet's disease and immunomodulant treatment approaches.
Salmaninejad, A, Gowhari, A, Hosseini, S, Aslani, S, Yousefi, M, Bahrami, T, Ebrahimi, M, Nesaei, A, Zal, M
Journal of immunotoxicology. 2017;(1):137-151
Abstract
Behçet's disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD.
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10.
Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review.
Martelli, L, Olivera, P, Roblin, X, Attar, A, Peyrin-Biroulet, L
Journal of gastroenterology. 2017;(1):19-25
Abstract
BACKGROUND Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. METHODS All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. RESULTS Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to €13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. CONCLUSIONS Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.